Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; John Paul II Hospital, Krakow, Poland.
Department of Adult Congenital Heart Diseases, Institute of Cardiology, Warsaw, Poland.
J Thorac Cardiovasc Surg. 2014 Apr;147(4):1284-90. doi: 10.1016/j.jtcvs.2013.06.011. Epub 2013 Jul 24.
Thrombosis occurs in up to 30% of patients with various forms of congenital single ventricle after the Fontan procedure. We investigated hemostatic abnormalities in adult Fontan patients.
Forty-eight Fontan patients between ages 18 and 40 years, including 10 (21%) patients with previous thromboembolism 5 to 15 years after surgery, and 35 control subjects matched for age and sex were studied. Coagulation factors and inhibitors, together with markers of fibrinolysis, platelets, and endothelial activation, were determined in peripheral venous blood plasma.
Compared with control subjects, Fontan patients showed lower, although mostly within normal ranges, values of all coagulation factors, as well as reduced free protein S, in association with higher antithrombin and free tissue factor pathway inhibitor levels. Thrombin generation, reflected by prothrombin fragment 1.2, and platelet activation markers were increased in Fontan patients. The plasma clot lysis time was prolonged in Fontan patients, which was associated with an increased activity of thrombin-activatable fibrinolysis inhibitor. Fontan patients with previous thromboembolism had lower oxygen saturation, coagulation factors V and VIII, and free protein S, and increased von Willebrand factor, soluble CD40 ligand, and P-selectin. Other laboratory or clinical parameters were not associated with prior thrombotic episodes.
Adult Fontan patients are characterized by enhanced platelet activation and endothelial injury, heightened thrombin formation, and impaired fibrinolysis. Patients showed reduced free protein S levels, increased platelet activation, and endothelial damage after thromboembolic events observed late after Fontan surgery. Our findings indicate novel prothrombotic mechanisms in adult Fontan patients, which might help to optimize thromboprophylaxis.
在 Fontan 手术后，各种形式的先天性单心室患者中，多达 30%发生血栓形成。我们研究了成年 Fontan 患者的止血异常。
研究了 48 名年龄在 18 至 40 岁之间的 Fontan 患者，包括 10 名（21%）在手术后 5 至 15 年内有过血栓栓塞史的患者，以及 35 名年龄和性别匹配的对照患者。在周围静脉血浆中测定凝血因子和抑制剂，以及纤溶、血小板和内皮细胞激活的标志物。
与对照患者相比，Fontan 患者的所有凝血因子值均较低，尽管大多数仍在正常范围内，并且游离蛋白 S 减少，同时抗凝血酶和游离组织因子途径抑制剂水平升高。Fontan 患者的凝血酶生成（反映为凝血酶原片段 1.2）和血小板激活标志物增加。Fontan 患者的血浆凝块溶解时间延长，这与凝血酶激活的纤溶抑制剂活性增加有关。有过血栓栓塞史的 Fontan 患者的氧饱和度、凝血因子 V 和 VIII 以及游离蛋白 S 降低，而血管性血友病因子、可溶性 CD40 配体和 P-选择素增加。其他实验室或临床参数与先前的血栓形成事件无关。
成年 Fontan 患者的特征是血小板激活和内皮损伤增强、凝血酶形成增加以及纤溶受损。在 Fontan 手术后晚期发生血栓栓塞事件的患者中，Fontan 患者的游离蛋白 S 水平降低、血小板激活增加和内皮损伤。我们的研究结果表明，成年 Fontan 患者存在新的促血栓形成机制，这可能有助于优化血栓预防。
